Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 72 Records) |
Query Trace: Cooley L[original query] |
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Rate and durability of clearance of hepatitis B surface antigen in Alaska Native persons with long-term hepatitis B virus infection: 1982-2019
Bruden D , McMahon BJ , Snowball M , Towshend-Bulson L , Homan C , Johnston JM , Simons BC , Bruce MG , Cooley L , Spradling PR , Harris AM . Hepatology 2024 79 (6) 1412-1420 BACKGROUND AND AIMS: A functional cure and therapeutic end point of chronic HBV infection is defined as the clearance of HBsAg from serum. Little is known about the long-term durability of HBsAg loss in the Alaskan Native population. APPROACH AND RESULTS: We performed a retrospective cohort study of Alaska Native patients with chronic HBV-monoinfection from January 1982 through December 2019. The original group in this cohort was identified during a 1982 to 1987 population-based screening for 3 HBV serologic markers in 53,000 Alaska Native persons. With close to 32,000 years of follow-up, we assessed the frequency and duration of HBsAg seroclearance (HBsAg-negative for > 6 mo). We examined factors associated with HBsAg clearance and followed persons for a median of 13.1 years afterward to assess the durability of HBsAg clearance. Among 1079 persons with an average length of follow-up of 33 years, 260 (24%) cleared HBsAg at a constant rate of 0.82% per person/per year. Of the 260 persons who cleared, 249 (96%) remained HBsAg-negative, while 11 persons had ≥ 2 transient HBsAg-positive results in subsequent follow-up. CONCLUSIONS: Of the patients with chronic HBV monoinfection, 0.82% of people per year achieved a functional cure. HBsAg seroclearance was durable for treated and nontreated patients and lasted, on average, over 13 years without seroreversion. |
Anti-filarial antibodies are sensitive indicators of lymphatic filariasis transmission and enable identification of high-risk populations and hotspots
Lawford H , Mayfield H , Sam FA , Viali S , Kamu T , Cooley G , Simon A , Martin D , Lau CL . Int J Infect Dis 2024 107194 OBJECTIVES: Circulating filarial antigen (Ag) is used by elimination programs to monitor lymphatic filariasis (LF) transmission; however, antifilarial antibodies (Ab) may be more sensitive than Ag for detecting LF. Our objectives were to describe Ab seroprevalence, identify risk factors for Ab seropositivity, investigate age-specific associations between Ag and Ab, and evaluate geographic clustering of seropositivity. METHODS: Community-based serosurveys of participants aged ≥5 years were conducted in 35 primary sampling units (PSUs). Ag-positivity was detected using Alere™ Filariasis Test Strips and Ab-seropositivity using multiplex bead assays. Seroprevalence was adjusted for study design. RESULTS: Of 3795 participants (range:5-90 years), adjusted prevalence for Ag, Bm14 Ab, Wb123 Ab, and Bm33 Ab were 3.7% (n=117), 20.3% (n=583), 32.2% (n=987), and 51.0% (n=1659), respectively. Male sex, older age, and residents of suspected hotspots had higher odds of seropositivity to all seromarkers. Seroprevalence was lower in 5-9-year-olds vs ≥10-year-olds (p<0.001). Clustering was significantly higher in households (intra-cluster correlation for Ag:0.45; Bm14 Ab:0.32; Bm33 Ab:0.31; Wb123 Ab:0.29) compared to PSUs or region. CONCLUSIONS: Abs enabled identification of risk factors for seropositivity and geographical clustering to inform targeted interventions for LF programmes. Further research is needed to define Ab thresholds for active versus past infection and elimination targets. |
Testing trends and co-testing patterns for HIV, hepatitis C and sexually transmitted infections (STIs) in Emergency departments
Symum H , Van Handel M , Sandul A , Hutchinson A , Tsang CA , Pearson WS , Delaney KP , Cooley LA , Gift TL , Hoover KW , Thompson WW . Preventive Med Reports 2024 44 Background: Many underserved populations use Emergency Department (EDs) as primary sources of care, representing an important opportunity to provide infectious disease testing and linkage to care. We explored national ED testing trends and co-testing patterns for HIV, hepatitis C, and sexually transmitted infections (STIs). Methods: We used 2010–2019 Healthcare Cost and Utilization Project, Nationwide Emergency Department Sample data to estimate ED visit testing rates for HIV, hepatitis C, chlamydia, gonorrhea, and syphilis infections, identified by Current Procedural Terminology codes. Trends and co-testing (visit with tests for > 1 infection) patterns were analyzed by sociodemographic, hospital, and visit characteristics. Trends were evaluated as the average annual percentage change (AAPC) using the Joinpoint Regression. Results: During 2010–2019, testing events per 1000 visits (AAPCs) increased for HIV from 1.3 to 4.2 (16.3 %), hepatitis C from 0.4 to 2.2 (25.1 %), chlamydia from 9.1 to 16.0 (6.6 %), gonorrhea from 8.4 to 15.7 (7.4 %), and syphilis from 0.7 to 2.0 (12.9 %). Rate increases varied by several characteristics across infections. The largest AAPC increases were among visits by groups with lower base rate testing in 2010, including persons aged ≥ 65 years (HIV: 36.4 %), with Medicaid (HIV: 43.8 %), in the lowest income quintile (hepatitis C: 36.9 %), living in the West (syphilis: 49.4 %) and with non-emergency diagnoses (hepatitis C: 44.1 %). Co-testing increased significantly for all infections except hepatitis C. Conclusions: HIV, hepatitis C, and STI testing increased in EDs during 2010–2019; however, co-testing patterns were inconsistent. Co-testing may improve diagnosis and linkage to care, especially in areas experiencing higher rates of infection. © 2024 |
shinyMBA: a novel R shiny application for quality control of the multiplex bead assay for serosurveillance studies
Matson Z , Cooley G , Parameswaran N , Simon A , Bankamp B , Coughlin MM . Sci Rep 2024 14 (1) 7442 The multiplex bead assay (MBA) based on Luminex xMAP technology can be used as a tool to measure seroprevalence as part of population immunity evaluations to multiple antigens in large-scale serosurveys. However, multiplexing several antigens presents challenges for quality control (QC) assessments of the data because multiple parameters must be evaluated for each antigen. MBA QC parameters include monitoring bead counts and median fluorescence intensity (MFI) for each antigen in plate wells, and performance of assay controls included on each plate. Analyzing these large datasets to identify plates failing QC standards presents challenges for many laboratories. We developed a novel R Shiny application, shinyMBA, to expedite the MBA QC processes and reduce the risk of user error. The app allows users to rapidly merge multi-plate assay outputs to evaluate bead count, MFI, and performance of assay controls using statistical process control charts for all antigen targets simultaneously. The utility of the shinyMBA application and its various outputs are demonstrated using data from 32 synthetic xPONENT files with 3 multiplex antigens and two population serosurveillance studies that evaluated 1200 and 3871 samples, respectively, for 20 multiplexed antigens. The shinyMBA open-source code is available for download and modification at https://github.com/CDCgov/shinyMBA . Incorporation of shinyMBA into Luminex serosurveillance workflows can vastly improve the speed and accuracy of QC processes. |
Genomic and phenotypic characterization of shiga toxin-producing Escherichia albertii strains isolated from wild birds in a major agricultural region in California
Carter MQ , Quiñones B , He X , Pham A , Carychao D , Cooley MB , Lo CC , Chain PSG , Lindsey RL , Bono JL . Microorganisms 2023 11 (11) Escherichia albertii is an emerging foodborne pathogen. To better understand the pathogenesis and health risk of this pathogen, comparative genomics and phenotypic characterization were applied to assess the pathogenicity potential of E. albertii strains isolated from wild birds in a major agricultural region in California. Shiga toxin genes stx(2f) were present in all avian strains. Pangenome analyses of 20 complete genomes revealed a total of 11,249 genes, of which nearly 80% were accessory genes. Both core gene-based phylogenetic and accessory gene-based relatedness analyses consistently grouped the three stx(2f)-positive clinical strains with the five avian strains carrying ST7971. Among the three Stx2f-converting prophage integration sites identified, ssrA was the most common one. Besides the locus of enterocyte effacement and type three secretion system, the high pathogenicity island, OI-122, and type six secretion systems were identified. Substantial strain variation in virulence gene repertoire, Shiga toxin production, and cytotoxicity were revealed. Six avian strains exhibited significantly higher cytotoxicity than that of stx(2f)-positive E. coli, and three of them exhibited a comparable level of cytotoxicity with that of enterohemorrhagic E. coli outbreak strains, suggesting that wild birds could serve as a reservoir of E. albertii strains with great potential to cause severe diseases in humans. |
Strain of multidrug-resistant salmonella newport remains linked to travel to Mexico and U.S. beef products - United States, 2021-2022
Ford L , Ellison Z , Schwensohn C , Griffin I , Birhane MG , Cote A , Fortenberry GZ , Tecle S , Higa J , Spencer S , Patton B , Patel J , Dow J , Maroufi A , Robbins A , Donovan D , Fitzgerald C , Burrell S , Tolar B , Folster JP , Cooley LA , Francois Watkins LK . MMWR Morb Mortal Wkly Rep 2023 72 (45) 1225-1229 In 2016, CDC identified a multidrug-resistant (MDR) strain of Salmonella enterica serotype Newport that is now monitored as a persisting strain (REPJJP01). Isolates have been obtained from U.S. residents in all 50 states and the District of Columbia, linked to travel to Mexico, consumption of beef products obtained in the United States, or cheese obtained in Mexico. In 2021, the number of isolates of this strain approximately doubled compared with the 2018-2020 baseline and remained high in 2022. During January 1, 2021- December 31, 2022, a total of 1,308 isolates were obtained from patients, cattle, and sheep; 86% were MDR, most with decreased susceptibility to azithromycin. Approximately one half of patients were Hispanic or Latino; nearly one half reported travel to Mexico during the month preceding illness, and one third were hospitalized. Two multistate outbreak investigations implicated beef products obtained in the United States. This highly resistant strain might spread through travelers, animals, imported foods, domestic foods, or other sources. Isolates from domestic and imported cattle slaughtered in the United States suggests a possible source of contamination. Safe food and drink consumption practices while traveling and interventions across the food production chain to ensure beef safety are necessary in preventing illness. |
Enteropathogen antibody dynamics and force of infection among children in low-resource settings (preprint)
Arnold BF , Martin DL , Juma J , Mkocha H , Ochieng JB , Cooley GM , Omore R , Goodhew EB , Morris JF , Costantini V , Vinje J , Lammie PJ , Priest JW . bioRxiv 2019 522920 Little is known about enteropathogen seroepidemiology among children in low-resource settings. We measured serological IgG responses to eight enteropathogens (Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, enterotoxigenic Escherichia coli, Vibrio cholerae, Campylobacter jejuni, norovirus) in cohorts from Haiti, Kenya, and Tanzania. We studied antibody dynamics and force of infection across pathogens and cohorts. Enteropathogens shared common seroepidemiologic features that enabled between-pathogen comparisons of transmission. Overall, exposure was intense: for most pathogens the window of primary infection was <3 years old; for highest transmission pathogens primary infection occurred within the first year. Longitudinal profiles revealed significant IgG boosting and waning above seropositivity cutoffs, underscoring the value of longitudinal designs to estimate force of infection. Seroprevalence and force of infection were rank-preserving across pathogens, illustrating the measures provide similar information about transmission heterogeneity. Our findings suggest multiplex antibody assays are a promising approach to measure population-level enteropathogen transmission in serologic surveillance. |
A perilous combination: Streptococcus coinfection with human plague-report of two cases and review of the literature, 1937-2022
Erly B , Fleck-Derderian S , Cooley KM , Meyer-Lee K , House J , VinHatton E , Nelson CA . Vector Borne Zoonotic Dis 2023 23 (7) 371-377 Background: Plague in humans and animals is caused by Yersinia pestis, a zoonotic gram-negative bacterium endemic in certain regions of Asia, Africa, and the United States. Coinfection with both Y. pestis and Streptococci species has been anecdotally reported in humans and associated with severe and rapidly fatal disease. Methods: This report presents two cases of patients who died following Y. pestis and Streptococcus coinfection. Additional cases of previously published Y. pestis-Streptococcus coinfection were identified and reviewed using a search of electronic databases. Results: The first case patient developed cough and dyspnea following 4 days of fever, malaise, and back pain and died before receiving medical care. Postmortem blood cultures were positive for Y. pestis, Streptococcus pyogenes, and Streptococcus dysgalactiae. The second case patient was hospitalized with fever, vomiting, diarrhea, and dyspnea and died of sepsis and respiratory failure on the day of admission. Y. pestis and Streptococcus pneumoniae were isolated from blood cultures drawn on admission. Seven additional cases of Y. pestis and Streptococcus coinfection were identified, dating between 1948 and 2009. These patients were healthy overall before their illness, with ages ranging from 9 to 60 years. The majority of patients had primary bubonic plague with associated pneumonia or septicemia. None of the patients who died received timely antimicrobial therapy directed against gram-negative pathogens. In every case but one, an occupational or environmental risk factor for plague was later identified. Conclusion: Y. pestis infection begins with a pre-inflammatory phase, during which Y. pestis and other pathogens can rapidly proliferate. Streptococci, which are frequently asymptomatic colonizers, may become invasive in this environment, leading to coinfection. The challenges of diagnosing Y. pestis in the context of coinfection may delay effective treatment. This case series and literature review illustrate the importance of clinicians remaining alert to environmental and occupational exposures in patients presenting with an infectious syndrome, especially in those who have an unexpectedly severe clinical presentation. |
Treponemal antibody seroprevalence using a multiplex bead assay from samples collected during the 2018 Nigeria HIV/AIDS indicator and impact survey: Searching for yaws in Nigeria
Guagliardo SAJ , Parameswaran N , Agala N , Abubakar A , Cooley G , Ye T , Kamb M , Mba N , William N , Greby S , Iriemenam N , Alagi M , Okoye M , Martin D . Am J Trop Med Hyg 2023 108 (5) 977-980 Yaws is a chronic, relapsing disease of skin, bone, and cartilage caused by Treponema pallidum subsp. pertenue. Yaws was last reported in Nigeria in 1996, although neighboring countries have recently reported cases. We investigated serological evidence for yaws among children aged 0-14 years in Nigeria by measuring antibodies to the treponemal antigens rp17 and TmpA in blood specimens from a 2018 nationally representative HIV survey using a multiplex bead assay. The presence of antibodies to both antigens ("double positive") likely reflects current or recent treponemal infection. Overall, 1.9% (610/31,549) of children had anti-TmpA antibodies, 1.5% (476/31,549) had anti-rp17 antibodies, and 0.1% (39/31,549) were double positive. Among households, 0.5% (84/18,021) had a double-positive child, with a clustering of double-positive children. Although numbers are low, identification of antibodies to both TmpA and rp17 may warrant investigation, including more granular epidemiologic and clinical data, to assess the potential for continuing yaws transmission in Nigerian children. |
Tetanus and diphtheria seroprotection among children younger than 15 years in Nigeria, 2018: Who are the unprotected children
Tohme RA , Scobie HM , Okunromade O , Olaleye T , Shuaib F , Jegede T , Yahaya R , Nnaemeka N , Lawal B , Egwuenu A , Parameswaran N , Cooley G , An Q , Coughlin M , Okposen BB , Adetifa I , Bolu O , Ihekweazu C . Vaccines (Basel) 2023 11 (3) Serological surveys provide an objective biological measure of population immunity, and tetanus serological surveys can also assess vaccination coverage. We undertook a national assessment of immunity to tetanus and diphtheria among Nigerian children aged <15 years using stored specimens collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey, a national cross-sectional household-based survey. We used a validated multiplex bead assay to test for tetanus and diphtheria toxoid-antibodies. In total, 31,456 specimens were tested. Overall, 70.9% and 84.3% of children aged <15 years had at least minimal seroprotection (≥0.01 IU/mL) against tetanus and diphtheria, respectively. Seroprotection was lowest in the north west and north east zones. Factors associated with increased tetanus seroprotection included living in the southern geopolitical zones, urban residence, and higher wealth quintiles (p < 0.001). Full seroprotection (≥0.1 IU/mL) was the same for tetanus (42.2%) and diphtheria (41.7%), while long-term seroprotection (≥1 IU/mL) was 15.1% for tetanus and 6.0% for diphtheria. Full- and long-term seroprotection were higher in boys compared to girls (p < 0.001). Achieving high infant vaccination coverage by targeting specific geographic areas and socio-economic groups and introducing tetanus and diphtheria booster doses in childhood and adolescence are needed to achieve lifelong protection against tetanus and diphtheria and prevent maternal and neonatal tetanus. |
Lessons learned from the implementation of integrated serosurveillance of communicable diseases in the Americas
Saboyá-Díaz MI , Castellanos LG , Morice A , Ade MP , Rey-Benito G , Cooley GM , Scobie HM , Wiegand RE , Coughlin MM , Martin DL . Rev Panam Salud Publica 2023 47 e53 OBJECTIVE: Systematize the experience and identify challenges and lessons learned in the implementation of an initiative for integrated serosurveillance of communicable diseases using a multiplex bead assay in countries of the Americas. METHODS: Documents produced in the initiative were compiled and reviewed. These included concept notes, internal working papers, regional meetings reports, and survey protocols from the three participating countries (Mexico, Paraguay, and Brazil) and two additional countries (Guyana and Guatemala) where serology for several communicable diseases was included in neglected tropical diseases surveys. Information was extracted and summarized to describe the experience and the most relevant challenges and lessons learned. RESULTS: Implementing integrated serosurveys requires interprogrammatic and interdisciplinary work teams for the design of survey protocols to respond to key programmatic questions aligned to the needs of the countries. Valid laboratory results are critical and rely on the standardized installment and roll-out of laboratory techniques. Field teams require adequate training and supervision to properly implement survey procedures. The analysis and interpretation of serosurveys results should be antigen-specific, contextualizing the responses for each disease, and triangulated with programmatic and epidemiological data for making decisions tailored to specific population socioeconomic and ecologic contexts. CONCLUSIONS: Integrated serosurveillance as a complementary tool for functional epidemiological surveillance systems is feasible to use and key components should be considered: political engagement, technical engagement, and integrated planning. Aspects such as designing the protocol, selecting target populations and diseases, laboratory capacities, anticipating the capacities to analyze and interpret complex data, and how to use it are key. |
Plague meningitis: A systematic review of clinical course, antimicrobial treatment, and outcomes
Cooley KM , Fleck-Derderian S , McCormick DW , Nelson CA . Health Secur 2022 21 (1) 22-33 Plague meningitis is a serious and often fatal manifestation of Yersinia pestis infection. In the aftermath of a bioweapon attack with Y pestis, this typically rare manifestation may develop in a substantial number of patients, particularly if treatment delays occur. Risk factors, clinical evolution, and optimal treatment strategies for plague meningitis are not well understood. We searched PubMed Central and other databases for reports of plague meningitis in any language. Articles containing descriptions of patients with plague meningitis and outcome were included. Among 1,496 articles identified in our search, 56 articles describing 84 cases from 1898 to 2015 met inclusion criteria. The median age of patients was 16 years (range 6 weeks to 64 years); 68% were male. Most patients (n = 50, 60%) developed meningitis following primary bubonic plague. Common signs and symptoms included fever (n = 56, 66%), nuchal rigidity (n = 38, 45%), and headache (n = 33, 36%); 29% (n = 24) of patients had focal neurologic deficits such as cranial nerve abnormalities. Almost all (n = 23, 96%) of the 24 patients who did not receive antimicrobials died, and 42% (n = 25) of the 59 patients treated with antimicrobials died. The case fatality rate of patients grouped by antimicrobial received was 50% (1 out of 2) for fluoroquinolones, 19% (4 out of 21) for aminoglycosides, 14% (2 out of 14) for sulfonamides, 11% (2 out of 18) for chloramphenicol, and 0% (0 out of 13) for tetracyclines. Plague meningitis most often occurs as a complication of bubonic plague and can cause focal neurologic deficits. Survival is more likely in patients who receive antimicrobials; tetracyclines, aminoglycosides, and chloramphenicol had the lowest associated case fatality rates. |
Recent incarceration among individuals infected with hepatitis A virus during person-to-person community outbreaks, United States, 2016-2020
Hagan LM , Montgomery MP , Lauro PL , Cima M , Stringer G , Kupferman NM , Leapley A , Gandhi AP , Nims D , Iberg Johnson J , Bouton L , Burkholder C , Grilli GA , Kittle T , Hansen K , Sievers MM , Newman AP , Albertson JP , Taylor B , Pietrowski M , Stous S , Qiu-Shultz Z , Jones C , Barbeau B , Nicolai LA , McCombs K , Chan M , Cooley L , Gupta N , Nelson N . Public Health Rep 2022 138 (4) 333549221108413 OBJECTIVES: Although many people who are incarcerated have risk factors for hepatitis A virus (HAV) infection, the proportion of hepatitis A cases among people with a recent incarceration is unknown. We examined the relationship between recent incarceration and HAV infection during community-based, person-to-person outbreaks to inform public health recommendations. METHODS: The Centers for Disease Control and Prevention surveyed health departments in 33 jurisdictions reporting person-to-person HAV outbreaks during 2016-2020 on the number of outbreak-associated cases, HAV-infected people recently incarcerated, and HAV-associated hospitalizations and deaths. RESULTS: Twenty-five health departments reported 18 327 outbreak-associated hepatitis A cases during January 11, 2016-January 24, 2020. In total, 2093 (11.4%) HAV-infected people had been recently incarcerated. Of those with complete data, 1402 of 1462 (95.9%) had been held in a local jail, and 1513 of 1896 (79.8.%) disclosed hepatitis A risk factors. Eighteen jurisdictions reported incarceration timing relative to the exposure period. Of 9707 cases in these jurisdictions, 991 (10.2%) were among recently incarcerated people; 451 of 688 (65.6%) people with complete data had been incarcerated during all (n = 55) or part (n = 396) of their exposure period. CONCLUSIONS: Correctional facilities are important settings for reaching people with risk factors for HAV infection and can also be venues where transmission occurs. Providing HAV vaccination to incarcerated people, particularly people housed in jails, can be an effective component of community-wide outbreak response. |
Plague in disguise: The discovery of occult buboes on surgical procedure or autopsy
Fleck-Derderian S , Cooley KM , Nelson CA . Vector Borne Zoonotic Dis 2022 22 (4) 225-231 Introduction: Bubonic plague classically manifests as a painful, swollen superficial lymph node (bubo) that is readily apparent on physical examination. However, patients occasionally present with buboes formed in deep lymph nodes, which are difficult to detect and can lead to delays in diagnosis and treatment. To better characterize this phenomenon, we conducted a review of the published literature to identify reports of occult buboes among patients with plague. Methods: Articles were identified from two sources: a systematic review on plague treatment, and a search of the PubMed Central database. Articles were eligible if they described a patient with plague who had (1) no evidence of lymphadenopathy on examination; and (2) at least one bubo discovered during surgery or autopsy. Results: Six patients with occult buboes were identified among 5120 articles screened. The majority were male (n = 4/6) and three were <15 years of age. Fever (n = 6/6), leukocytosis (n = 5/6), and abdominal pain or distention (n = 4/6) were the most common signs and symptoms. Initial diagnoses included other bacterial infections, appendicitis, or acute abdomen. Four patients received at least one antimicrobial effective against Yersinia pestis; however, some experienced delayed treatment due to late diagnosis of plague. Occult buboes were discovered in retroperitoneal (n = 2), inguinal/femoral (n = 2), mesenteric (n = 2), axillary (n = 1), and mediastinal (n = 1) regions. Four of the six patients died. Conclusions: Patients with occult buboes experienced delays in the diagnosis of plague and a high fatality rate. Clinicians in plague-endemic areas should consider the presence of occult buboes among patients with compatible symptoms and exposure history. |
Development of a Bead-Based Multiplex Assay for Use in Multianalyte Screening and Surveillance of HIV, Viral Hepatitis, Syphilis, and Herpes.
Yufenyuy EL , Vedapuri S , Zheng A , Cooley G , Danavall D , Mayur S , Kodani M , Chen C , Tun Y , Fakile YF , Martin D , Kamili S , Karem K , Parekh BS . J Clin Microbiol 2022 60 (5) e0234821 Diagnostic assays that can simultaneously determine the presence of infection with multiple pathogens are key for diagnosis and surveillance. Current multiplex diagnostic assays are complex and often have limited availability. We developed a simple, multianalyte, pathogen detection assay for screening and serosurveillance using the Luminex Magpix platform that is high throughput and can be helpful in monitoring multiple diseases. The Luminex bead-based 10-plex immunoassay for the detection of HIV-1, HIV-2, Treponema pallidum, hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus 1 (HSV-1), and HSV-2 infections was accomplished by coupling beads with specific antigens to detect IgG antibodies in plasma or serum samples. Each coupled antigen was systematically optimized, and the performance was evaluated using a panel of well-characterized specimens (n=417) that contained antibodies to HIV-1, HIV-2, T. pallidum, HBV, HCV, HSV-1, and HSV-2. The multiplex assay had a sensitivity of 92.2% (95% Clopper-Pearson confidence interval [CI], 90.2 to 94.0%) and a specificity of 98.1% (95% CI, 97.6 to 98.7%). The sensitivities and specificities for disease-specific biomarker detection ranged from 68.7 to 100% and 95.6 to 100%, respectively. The results showed that the 10-plex immunoassay had an overall agreement of 96.7% (95% CI, 96.7 to 97.3%) with reference tests and a corresponding kappa value of 0.91 (95% CI, 0.90 to 0.93). Kappa values for the individual pathogens ranged from 0.69 to 1.00. The assay is robust and allows the simultaneous detection of antibodies to multiple antigens using a small sample volume in a high-throughput format. This assay has the potential to simplify disease surveillance by providing an alternative to expensive and highly specialized individual tests. |
Diphtheria and tetanus seroepidemiology among children in Ukraine, 2017
Khetsuriani N , Zaika O , Slobodianyk L , Scobie HM , Cooley G , Dimitrova SD , Stewart B , Geleishvili M , Allahverdiyeva V , O'Connor P , Huseynov S . Vaccine 2022 40 (12) 1810-1820 BACKGROUND: The drastic decline of Ukraine's immunization coverage since 2009 led to concerns about potential resurgence diphtheria and tetanus, along with other vaccine-preventable diseases. METHODS: To assess population immunity against diphtheria and tetanus, we tested specimens from the serosurvey conducted in 2017 among children born in 2006-2015, the birth cohorts targeted by the nationwide outbreak response immunization following a circulating vaccine-derived poliovirus type 1 outbreak in Zakarpattya province in 2015. We surveyed four regions of Ukraine, using cluster sampling in Zakarpattya, Sumy, and Odessa provinces and simple random sampling in Kyiv City. We tested serum specimens for IgG antibodies against diphtheria and tetanus, using microbead assays (MBA). We estimated seroprevalence and calculated 95% confidence intervals. We also obtained information on the immunization status of surveyed children. RESULTS: Seroprevalence of 0.1IU/mL diphtheria antibodies was <80% in all survey sites (50.0%-79.2%). Seroprevalence of 0.1IU/mL tetanus antibodies was 80% in Sumy, Kyiv City, and Odessa (80.2%-89.1%) and 61.6% in Zakarpattya. Across the sites, the proportion of children vaccinated age-appropriately with diphtheria-tetanus-containing vaccines (DTCV) was 28.5%-57.4% among children born in 2006-2010 and 34.1%-54.3% among children born in 2011-2015. The proportion of recipients of<3 DTCV doses increased from 7.1%-16.7% among children born in 2006-2010 to 19.8%-38.6% among children born in 2011-2015, as did the proportion of recipients of zero DTCV doses (2.6%-8.8% versus 8.0%-14.0%, respectively). CONCLUSIONS: Protection against diphtheria among children born in 2006-2015 was suboptimal (<80%), particularly in Zakarpattya. Protection against tetanus was adequate (80%) except in Zakarpattya. Diphtheria-tetanus immunization status was suboptimal across all sites. Catch-up vaccination of unvaccinated/under-vaccinated children and other efforts to increase immunization coverage would close these immunity gaps and prevent the resurgence of diphtheria and tetanus in Ukraine, particularly in Zakarpattya. |
Strategies for successful vaccination among two medically underserved populations: Lessons learned from hepatitis A outbreaks
Montgomery MP , Eckert M , Hofmeister MG , Foster MA , Weng MK , Augustine R , Gupta N , Cooley LA . Am J Public Health 2021 111 (8) 1409-1412 Traditional models of preventive care rely heavily on delivering services in established clinical settings. These settings might provide incomplete access for certain medically underserved populations, such as people who use drugs (PWUD), people experiencing homelessness (PEH), and people who are incarcerated or detained, because of either barriers in accessing care or past experiences of stigma and discrimination. Missed opportunities for delivering preventive vaccination services to medically underserved populations can lead to increased transmission, morbidity, and mortality. Between 2016 and 2021, widespread person-to-person outbreaks of hepatitis A across the United States—disproportionately affecting PWUD and PEH—highlighted both the challenges encountered and innovative solutions required in bringing preventive services to medically underserved populations. 1 |
Parasitic disease surveillance, Mississippi, USA
Bradbury RS , Lane M , Handali S , Cooley G , Montgomery SP . Emerg Infect Dis 2021 27 (8) 2201-2204 Surveillance for soil-transmitted helminths, strongyloidiasis, cryptosporidiosis, and giardiasis was conducted in Mississippi, USA. PCR performed on 224 fecal samples for all soil-transmitted helminths and on 370 samples for only Necator americanus and Strongyloides stercoralis identified 1 S. stercoralis infection. Seroprevalences were 8.8% for Toxocara, 27.4% for Cryptosporidium, 5.7% for Giardia, and 0.2% for Strongyloides parasites. |
Modeling future climate suitability for the western blacklegged tick, Ixodes pacificus, in California with an emphasis on land access and ownership
Hahn MB , Feirer S , Monaghan AJ , Lane RS , Eisen RJ , Padgett KA , Kelly M . Ticks Tick Borne Dis 2021 12 (5) 101789 In the western United States, Ixodes pacificus Cooley & Kohls (Acari: Ixodidae) is the primary vector of the agents causing Lyme disease and granulocytic anaplasmosis in humans. The geographic distribution of the tick is associated with climatic variables that include temperature, precipitation, and humidity, and biotic factors such as the spatial distribution of its primary vertebrate hosts. Here, we explore (1) how climate change may alter the geographic distribution of I. pacificus in California, USA, during the 21(st) century, and (2) the spatial overlap among predicted changes in tick habitat suitability, land access, and ownership. Maps of potential future suitability for I. pacificus were generated by applying climate-based species distribution models to a multi-model ensemble of climate change projections for the Representative Concentration Pathway (RCP) 4.5 (moderate emission) and 8.5 (high emission) scenarios for two future periods: mid-century (2026-2045) and end-of-century (2086-2099). Areas climatically-suitable for I. pacificus are projected to expand by 23% (mid-century RCP 4.5) to 86% (end-of-century RCP 8.5) across California, compared to the historical period (1980-2014), with future estimates of total suitable land area ranging from about 88 to 133 thousand km(2), or up to about a third of California. Regions projected to have the largest area increases in suitability by end-of-century are in northwestern California and the south central and southern coastal ranges. Over a third of the future suitable habitat is on lands currently designated as open access (i.e. publicly available), and by 2100, the amount of these lands that are suitable habitat for I. pacificus is projected to more than double under the most extreme emissions scenario (from ~23,000 to >51,000 km(2)). Of this area, most is federally-owned (>45,000 km(2)). By the end of the century, 26% of all federal land in the state is predicted to be suitable habitat for I. pacificus. The resulting maps may facilitate regional planning and preparedness by informing public health and vector control decision-makers. |
Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response
Nelson CA , Meaney-Delman D , Fleck-Derderian S , Cooley KM , Yu PA , Mead PS . MMWR Recomm Rep 2021 70 (3) 1-27 This report provides CDC recommendations to U.S. health care providers regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of plague. Yersinia pestis, the bacterium that causes plague, leads to naturally occurring disease in the United States and other regions worldwide and is recognized as a potential bioterrorism weapon. A bioweapon attack with Y. pestis could potentially infect thousands, requiring rapid and informed decision making by clinicians and public health agencies. The U.S. government stockpiles a variety of medical countermeasures to mitigate the effects of a bioterrorism attack (e.g., antimicrobials, antitoxins, and vaccines) for which the 21st Century Cures Act mandates the development of evidence-based guidelines on appropriate use. Guidelines for treatment and postexposure prophylaxis of plague were published in 2000 by a nongovernmental work group; since then, new human clinical data, animal study data, and U.S. Food and Drug Administration approvals of additional countermeasures have become available. To develop a comprehensive set of updated guidelines, CDC conducted a series of systematic literature reviews on human treatment of plague and other relevant topics to collect a broad evidence base for the recommendations in this report. Evidence from CDC reviews and additional sources were presented to subject matter experts during a series of forums. CDC considered individual expert input while developing these guidelines, which provide recommended best practices for treatment and prophylaxis of human plague for both naturally occurring disease and following a bioterrorism attack. The guidelines do not include information on diagnostic testing, triage decisions, or logistics involved in dispensing medical countermeasures. Clinicians and public health officials can use these guidelines to prepare their organizations, hospitals, and communities to respond to a plague mass-casualty event and as a guide for treating patients affected by plague. |
No Serological Evidence of Trachoma or Yaws Among Residents of Registered Camps and Makeshift Settlements in Cox's Bazar, Bangladesh
Cooley GM , Feldstein LR , Bennett SD , Estivariz CF , Weil L , Bohara R , Vandenent M , Mainul Hasan A , Akhtar MS , Uzzaman MS , Billah MM , Conklin L , Ehlman DC , Asiedu K , Solomon AW , Alamgir A , Flora MS , Martin DL . Am J Trop Med Hyg 2021 104 (6) 2031-2037 Successful achievement of global targets for elimination of trachoma as a public health problem and eradication of yaws will require control efforts to reach marginalized populations, including refugees. Testing for serologic evidence of transmission of trachoma and yaws in residents of registered camps and a Makeshift Settlement in Cox's Bazar District, Bangladesh, was added to a serosurvey for vaccine-preventable diseases (VPDs) conducted April-May 2018. The survey was primarily designed to estimate remaining immunity gaps for VPDs, including diphtheria, measles, rubella, and polio. Blood specimens from 1- to 14-year-olds from selected households were collected and tested for antibody responses against antigens from Treponema pallidum and Chlamydia trachomatis using a multiplex bead assay to evaluate for serologic evidence of the neglected tropical diseases (NTDs) yaws and trachoma, respectively. The prevalence of antibodies against two C. trachomatis antigens in children ranged from 1.4% to 1.5% for Pgp3 and 2.8% to 7.0% for CT694. The prevalence of antibody responses against both of two treponemal antigens (recombinant protein17 and treponemal membrane protein A) tested was 0% to 0.15% in two camps. The data are suggestive of very low or no transmission of trachoma and yaws, currently or previously, in children resident in these communities. This study illustrates how integrated serologic testing can provide needed data to help NTD programs prioritize limited resources. |
Detection of Genetic Variability in Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) Between and Within the Eastern and Western United States.
Hojgaard A , Osikowicz LM , Maes S , Eisen L , Eisen RJ . J Med Entomol 2021 58 (6) 2154-2160 Borrelia miyamotoi is a hard tick-associated relapsing fever spirochete that is geographically widespread in Ixodes spp. (Acari: Ixodidae) ticks, but typically occurs at low prevalence. Genetic variability has been described among strains derived from Asia, Europe, and North America, and among tick species that carry the infection, but little variability has been described within foci or tick species. Capitalizing on access to B. miyamotoi nucleic acid extracted from host-seeking Ixodes scapularis Say or Ixodes pacificus Cooley & Kohls from 16 states, we explored genetic variability based on sequence analysis of four amplicons described herein. Consistent with previous studies, we detected significant genetic differences between strains derived from I. scapularis (eastern United States) and I. pacificus (western United States) and identified two distinct sequences in the western United States (Am-West-1 and Am-West-2). Unique to this study, we identified two distinct sequences in the eastern United States (Am-East-1 and Am-East-2). Based on the 161 samples we analyzed, Am-East-1 was the only type represented in 50 B. miyamotoi-infected ticks collected from the Northeast (Vermont, Maine, New York, Connecticut, and Rhode Island), whereas ticks collected from the North-Central and Mid-Atlantic states harbored B. miyamotoi comprised of both Am-East-1 and Am-East-2. Further studies are needed to better characterize the phylogeography of B. miyamotoi and to discern if there are biologically meaningful differences among sequence types. To facilitate further exploration, we developed a polymerase chain reaction (PCR) assay designed to differentiate Am-East-1, Am-East-2, and Am-West sequence types without having to sequence the amplicon. |
Demographic, clinical, and epidemiologic characteristics of persons under investigation for Coronavirus Disease 2019-United States, January 17-February 29, 2020.
McGovern OL , Stenger M , Oliver SE , Anderson TC , Isenhour C , Mauldin MR , Williams N , Griggs E , Bogere T , Edens C , Curns AT , Lively JY , Zhou Y , Xu S , Diaz MH , Waller JL , Clarke KR , Evans ME , Hesse EM , Morris SB , McClung RP , Cooley LA , Logan N , Boyd AT , Taylor AW , Bajema KL , Lindstrom S , Elkins CA , Jones C , Hall AJ , Graitcer S , Oster AM , Fry AM , Fischer M , Conklin L , Gokhale RH . PLoS One 2021 16 (4) e0249901 BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), evolved rapidly in the United States. This report describes the demographic, clinical, and epidemiologic characteristics of 544 U.S. persons under investigation (PUI) for COVID-19 with complete SARS-CoV-2 testing in the beginning stages of the pandemic from January 17 through February 29, 2020. METHODS: In this surveillance cohort, the U.S. Centers for Disease Control and Prevention (CDC) provided consultation to public health and healthcare professionals to identify PUI for SARS-CoV-2 testing by quantitative real-time reverse-transcription PCR. Demographic, clinical, and epidemiologic characteristics of PUI were reported by public health and healthcare professionals during consultation with on-call CDC clinicians and subsequent submission of a CDC PUI Report Form. Characteristics of laboratory-negative and laboratory-positive persons were summarized as proportions for the period of January 17-February 29, and characteristics of all PUI were compared before and after February 12 using prevalence ratios. RESULTS: A total of 36 PUI tested positive for SARS-CoV-2 and were classified as confirmed cases. Confirmed cases and PUI testing negative for SARS-CoV-2 had similar demographic, clinical, and epidemiologic characteristics. Consistent with changes in PUI evaluation criteria, 88% (13/15) of confirmed cases detected before February 12, 2020, reported travel from China. After February 12, 57% (12/21) of confirmed cases reported no known travel- or contact-related exposures. CONCLUSIONS: These findings can inform preparedness for future pandemics, including capacity for rapid expansion of novel diagnostic tests to accommodate broad surveillance strategies to assess community transmission, including potential contributions from asymptomatic and presymptomatic infections. |
Mass SARS-CoV-2 Testing in a Dormitory-Style Correctional Facility in Arkansas.
Tompkins LK , Gunn JKL , Cherney B , Ham JE , Horth R , Rossetti R , Bower WA , Benson K , Hagan LM , Crist MB , Mettee Zarecki SL , Dixon MG , Dillaha JA , Patil N , Dusseau C , Ross T , Matthews HS , Garner K , Starks AM , Weiner Z , Bowen MD , Bankamp B , Newton AE , Logan N , Schuh AJ , Trimble S , Pfeiffer H , James AE , Tian N , Jacobs JR , Ruiz F , McDonald K , Thompson M , Cooley L , Honein MA , Rose DA . Am J Public Health 2021 111 (5) e1-e10 Objectives. To assess SARS-CoV-2 transmission within a correctional facility and recommend mitigation strategies.Methods. From April 29 to May 15, 2020, we established the point prevalence of COVID-19 among incarcerated persons and staff within a correctional facility in Arkansas. Participants provided respiratory specimens for SARS-CoV-2 testing and completed questionnaires on symptoms and factors associated with transmission.Results. Of 1647 incarcerated persons and 128 staff tested, 30.5% of incarcerated persons (range by housing unit = 0.0%-58.2%) and 2.3% of staff tested positive for SARS-CoV-2. Among those who tested positive and responded to symptom questions (431 incarcerated persons, 3 staff), 81.2% and 33.3% were asymptomatic, respectively. Most incarcerated persons (58.0%) reported wearing cloth face coverings 8 hours or less per day, and 63.3% reported close contact with someone other than their bunkmate.Conclusions. If testing remained limited to symptomatic individuals, fewer cases would have been detected or detection would have been delayed, allowing transmission to continue. Rapid implementation of mass testing and strict enforcement of infection prevention and control measures may be needed to mitigate spread of SARS-CoV-2 in this setting. (Am J Public Health. Published online ahead of print March 18, 2021: e1-e10. https://doi.org/10.2105/AJPH.2020.306117). |
CDC Deployments to State, Tribal, Local, and Territorial Health Departments for COVID-19 Emergency Public Health Response - United States, January 21-July 25, 2020.
Dirlikov E , Fechter-Leggett E , Thorne SL , Worrell CM , Smith-Grant JC , Chang J , Oster AM , Bjork A , Young S , Perez AU , Aden T , Anderson M , Farrall S , Jones-Wormley J , Walters KH , LeBlanc TT , Kone RG , Hunter D , Cooley LA , Krishnasamy V , Fuld J , Luna-Pinto C , Williams T , O'Connor A , Nett RJ , Villanueva J , Oussayef NL , Walke HT , Shugart JM , Honein MA , Rose DA . MMWR Morb Mortal Wkly Rep 2020 69 (39) 1398-1403 Coronavirus disease 2019 (COVID-19) is a viral respiratory illness caused by SARS-CoV-2. During January 21-July 25, 2020, in response to official requests for assistance with COVID-19 emergency public health response activities, CDC deployed 208 teams to assist 55 state, tribal, local, and territorial health departments. CDC deployment data were analyzed to summarize activities by deployed CDC teams in assisting state, tribal, local, and territorial health departments to identify and implement measures to contain SARS-CoV-2 transmission (1). Deployed teams assisted with the investigation of transmission in high-risk congregate settings, such as long-term care facilities (53 deployments; 26% of total), food processing facilities (24; 12%), correctional facilities (12; 6%), and settings that provide services to persons experiencing homelessness (10; 5%). Among the 208 deployed teams, 178 (85%) provided assistance to state health departments, 12 (6%) to tribal health departments, 10 (5%) to local health departments, and eight (4%) to territorial health departments. CDC collaborations with health departments have strengthened local capacity and provided outbreak response support. Collaborations focused attention on health equity issues among disproportionately affected populations (e.g., racial and ethnic minority populations, essential frontline workers, and persons experiencing homelessness) and through a place-based focus (e.g., persons living in rural or frontier areas). These collaborations also facilitated enhanced characterization of COVID-19 epidemiology, directly contributing to CDC data-informed guidance, including guidance for serial testing as a containment strategy in high-risk congregate settings, targeted interventions and prevention efforts among workers at food processing facilities, and social distancing. |
Parasitic Infection Surveillance in Mississippi Delta Children.
Bradbury RS , Arguello I , Lane M , Cooley G , Handali S , Dimitrova SD , Nascimento FS , Jameson S , Hellmann K , Tharp M , Byers P , Montgomery SP , Haynie L , Kirmse B , Pilotte N , Williams SA , Hobbs CV . Am J Trop Med Hyg 2020 103 (3) 1150-1153 Some recent studies suggest ongoing transmission of parasitic diseases in the American South; however, surveys in Mississippi children are lacking. We enrolled 166 children (median age 8 years, range 4-13 years) from the Mississippi Delta region and carried out multi-parallel real-time polymerase chain reaction (PCR) for Necator americanus, Ascaris lumbricoides, and Strongyloides stercoralis on their stool samples. Dried blood spots were obtained for multiplex serology antibody detection. Of 166 children, all reported having flushable toilets, 11% had soil exposure, and 34% had a pet dog or cat. None had prior diagnosis or treatment of parasitic disease. Multi-parallel real-time PCRs were negative on the 89 stool DNA extracts available for testing. Dried blood spot testing of all 166 children determined the seroprevalence of IgG antibodies to Toxocara spp. (3.6%), Cryptosporidium (2.4%), S. stercoralis, Fasciola hepatica, and Giardia duodenalis (all 0%). In conclusion, parasitic infections and exposure were scarce in this population. Larger studies of at-risk populations are needed. |
Seroprevalence of chronic hepatitis B virus infection and immunity to measles, rubella, tetanus and diphtheria among schoolchildren aged 6-7 years old in the Solomon Islands, 2016
Breakwell L , Anga J , Cooley G , Ropiti L , Gwyn S , Wannemuehler K , Woodring J , Ogaoga D , Martin D , Patel M , Tohme RA . Vaccine 2020 38 (30) 4679-4686 The Western Pacific Region (WPR) established a goal to decrease chronic hepatitis B virus (HBV) infection among children to <1% and to achieve >/=95% hepatitis B vaccine birth dose (HepB-BD) and >/=95% three-dose (HepB3) coverage by 2017. In 2016, we conducted a national serosurvey in the Solomon Islands among 6-7-year-old school children to assess progress towards the control goal and immunity to measles, rubella, tetanus and diphtheria. Eighty schools were selected systematically proportional to their 6-7-year-old population; all 6-7-year-olds were enrolled. We collected basic demographic information and vaccination history. Children were tested for HBV surface antigen (HBsAg) using a rapid test, and for immunity to measles, rubella, tetanus, and diphtheria using a multiplex bead assay. In total, 1,249 out of 1,492 children (84%) were enrolled, among whom 1,169 (94%) underwent HBsAg testing and 1,156 (93%) provided dried blood spots. Almost 80% (n = 982) of enrolled children had vaccination cards, among whom 59% (n = 584) received a timely HepB-BD (within 24 hours of birth), 95% (n = 932) received HepB3, and >90% received vaccines for diphtheria, tetanus, and measles (rubella vaccine was not available at the time). HBsAg prevalence was 3.1% (95% confidence interval (CI): 2.0%-4.9%), with 55% of identified cases from one province. Among 982 children with vaccination cards, HBsAg prevalence was higher among children who had not received a timely HepB-BD and at least two HepB doses compared to those who had (4% vs. 2%). Of 1,156 tested children, immunoprotection estimates were 99% (95% CI: 98%-99%) for measles, 99% (95% CI: 97%-100%) for rubella, 85% (95% CI: 83%-87%) for tetanus, and 51% (95% CI: 47%-55%) for diphtheria. Improving timely HepB-BD coverage and maintaining high HepB3 coverage could help Solomon Islands reach the regional HBV control goal. Low immunity to tetanus and diphtheria suggests the need to introduce booster doses to ensure long-term protection. |
Plague during pregnancy: A systematic review
Fleck-Derderian S , Nelson CA , Cooley KM , Russell Z , Godfred-Cato S , Oussayef NL , Oduyebo T , Rasmussen SA , Jamieson DJ , Meaney-Delman D . Clin Infect Dis 2020 70 S30-s36 BACKGROUND: Yersinia pestis continues to cause sporadic cases and outbreaks of plague worldwide and is considered a tier 1 bioterrorism select agent due to its potential for intentional use. Knowledge about the clinical manifestations of plague during pregnancy, specifically the maternal, fetal, and neonatal risks, is very limited. METHODS: We searched 12 literature databases, performed hand searches, and consulted plague experts to identify publications on plague during pregnancy. Articles were included if they reported a case of plague during pregnancy and at least 1 maternal or fetal outcome. RESULTS: Our search identified 6425 articles, of which 59 were eligible for inclusion and described 160 cases of plague among pregnant women. Most published cases occurred during the preantibiotic era. Among those treated with antimicrobials, the most commonly used were sulfonamides (75%) and streptomycin (54%). Among cases treated with antimicrobials, maternal mortality and fetal fatality were 29% and 62%, respectively; for untreated cases, maternal mortality and fetal fatality were 67% and 74%, respectively. Five cases demonstrated evidence of Y. pestis in fetal or neonatal tissues. CONCLUSIONS: Untreated Y. pestis infection during pregnancy is associated with a high risk of maternal mortality and pregnancy loss. Appropriate antimicrobial treatment can improve maternal survival, although even with antimicrobial treatment, there remains a high risk of pregnancy loss. Limited evidence suggests that maternal-fetal transmission of Y. pestis is possible, particularly in the absence of antimicrobial treatment. These results emphasize the need to treat or prophylax pregnant women with suspected plague with highly effective antimicrobials as quickly as possible. |
Treatment of human plague: A systematic review of published aggregate data on antimicrobial efficacy, 1939-2019
Godfred-Cato S , Cooley KM , Fleck-Derderian S , Becksted HA , Russell Z , Meaney-Delman D , Mead PS , Nelson CA . Clin Infect Dis 2020 70 S11-s19 BACKGROUND: Plague, caused by the bacterium Yersinia pestis, has killed millions in historic pandemics and continues to cause sporadic outbreaks. Numerous antimicrobials are considered effective for treating plague; however, well-defined information on the relative efficacy of various treatments is lacking. We conducted a systematic review of published data on antimicrobial treatment of plague reported in aggregate. METHODS: We searched databases including Embase, Medline, CINAHL, Cochrane Library, and others for publications with terms related to plague and antimicrobials. Articles were included if they contained 1) a group of patients treated for plague, with outcomes reported by antimicrobial regimen, and 2) laboratory evidence of Y. pestis infection or an epidemiologic link to patients with laboratory evidence of Y. pestis. Case fatality rate by antimicrobial regimen was calculated. RESULTS: In total, 5837 articles were identified; among these, 26 articles published between 1939 and 2008 met inclusion criteria. A total of 2631 cases of human plague reported within these articles were included. Among cases classified by primary clinical form of plague, 93.6% were bubonic, 5.9% pneumonic, and 0.5% septicemic with associated case fatalities of 14.2%, 31.1%, and 20.0%, respectively. Case fatality rate among patients who received monotherapy with tetracyclines, chloramphenicol, aminoglycosides, or sulfonamides was 1.3%, 1.4%, 7.5%, and 20.2%, respectively. Fluoroquinolones were only given as part of combination therapy. Penicillin was associated with a case fatality rate of 75%. CONCLUSIONS: Tetracyclines, chloramphenicol, and aminoglycosides were associated with the lowest case fatality rates of all antimicrobials used for treatment of plague. Additional research is needed to determine the efficacy of fluoroquinolones as monotherapy. |
Antimicrobial treatment of human plague: A systematic review of the literature on individual cases, 1937-2019
Nelson CA , Fleck-Derderian S , Cooley KM , Meaney-Delman D , Becksted HA , Russell Z , Renaud B , Bertherat E , Mead PS . Clin Infect Dis 2020 70 S3-s10 BACKGROUND: Yersinia pestis remains endemic in Africa, Asia, and the Americas and is a known bioterrorism agent. Treatment with aminoglycosides such as streptomycin or gentamicin is effective when initiated early in illness but can have serious side effects. Alternatives such as fluoroquinolones, tetracyclines, and sulfonamides are potentially safer but lack robust human data on efficacy. METHODS: We searched PubMed Central, Medline, Embase, and other databases for articles in any language with terms related to plague and antimicrobials. Articles that contained case-level information on antimicrobial treatment and patient outcome were included. We abstracted information related to patient demographics, clinical features, treatment, and fatality. RESULTS: Among 5837 articles screened, we found 762 published cases of treated plague reported from 1937 to 2019. Fifty-nine percent were male; median age was 22 years (range, 8 days-80 years). The case fatality rate was 20% overall. Most patients had primary bubonic (63%), pneumonic (21%), or septicemic (5%) plague, with associated case fatality rates of 17%, 27%, and 38%, respectively. Among those treated with an aminoglycoside (n = 407 [53%]), the case fatality rate was 13%. Among those treated with a sulfonamide (n = 322 [42%]), tetracycline (n = 171 [22%]), or fluoroquinolone (n = 61 [8%]), fatality was 23%, 10%, and 12%, respectively. Case fatality rate did not substantially differ between patients treated with 1 vs 2 classes of antimicrobials considered to be effective for plague. CONCLUSIONS: In addition to aminoglycosides, other classes of antimicrobials including tetracyclines, fluoroquinolones, and sulfonamides are effective for plague treatment, although publication bias and low numbers in certain treatment groups may limit interpretation. |
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